Potassium Carbonate → Formate

HRID 1051541Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH3:11])=[N:9][CH:10]=2)[CH:7]=1.[CH2:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][N:13]1[CH2:22][CH:23]([OH:41])[CH2:24][O:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=1.[C:42]([O-])([O-:44])=[O:43].[K+].[K+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH2:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][N:13]1[CH2:22][CH:23]([OH:41])[CH2:24][O:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([CH3:11])=[N:9][CH:10]=3)[CH:7]=2)[CH:27]=1.[CH:42]([O-:44])=[O:43]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 6-bromo-3-methylimidazo[1,5-a]pyridine (100 mg, 0.47 mmol), 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)propan-2-ol (211 mg, 0.52 mmol), K2CO3 (195 mg, 1.41 mmol) and Pd(dppf)Cl2 (10 mg) in a solution of dioxane (4 mL) and H2O (1 mL) was stirred at 120° C. for 30 minutes under microwave heating. The catalyst was filtered, the filtrate concentrated and the residue purified by Prep-HPLC to give the desired title product as a colorless oil and formate salt (15 mg, Yield 7%). 1H NMR (400 MHz, MeOD) δ 8.13 (s, 1H), 7.57 (d, J=4.8 Hz, 1H), 7.42 (dd, J=8.0 Hz, 1H), 7.31-7.11 (m, 7H), 7.09-7.00 (m, 2H), 4.53-4.49 (m, 1H), 4.42 (s, 2H), 4.15 (d, J=4.2 Hz, 2H), 3.57 (t, J=6.4 Hz, 2H), 3.43-3.36 (m, 2H), 3.18-3.16 (m, 2H), 2.68 (s, 3H). LCMS (m/z): 414.2 (M+1).

Workup

temperatureheating
filtrationThe catalyst was filtered
concentrationthe filtrate concentrated
customthe residue purified by Prep-HPLC

Sources & evidence

ORD record: ord-30cc9e10adce4b06893fc44bff46ccee
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09388173B2

Reaction notes

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